CNN  — 

Everywhere you look, the political news is good for Republicans.

President Joe Biden’s approval rating is stuck in the low 40s. Thirty House Democrats have already announced their plans to leave office at the end of the term. Republican enthusiasm is soaring.

And yet, Mitch McConnell is still nervous.

“People are thinking: Is there any way we can screw this up,” the Senate minority leader said on Tuesday. “Well, it’s always possible. And so part of my job is to try to prevent us from screwing this up by nominating people for the Senate who can win the primary, but can’t win the general.”

He’s not wrong! And there’s plenty of relatively recent history McConnell can point to as evidence of the dangers of picking the wrong nominee.

In 2010, Delaware Republicans opted for an unknown conservative named Christine O’Donnell rather than longtime GOP politician Mike Castle as their nominee. O’Donnell, who infamously ran an ad declaring that she was “not a witch,” lost to Democratic Sen. Chris Coons by a large margin in the general election.

Two years later, Missouri Republicans chose then-Rep. Todd Akin as their nominee. Akin quickly disqualified himself with comments about “legitimate rape.” Democratic Sen. Claire McCaskill won the general election easily.

Missouri – past and present – is likely on McConnell’s mind these days. With Republican Sen. Roy Blunt retiring, the current polling frontrunner in the race is former Gov. Eric Greitens.

The problem? Greitens resigned under pressure in 2018 after acknowledging an extramarital affair and facing allegations of blackmail, which he denied.

“It is not conservative to tie a woman up in your basement and assault her,” said Rep. Vicky Hartzler, who is also running for the seat, referring to Greitens’ scandal. (Greitens told CNN in a recent interview that he did “absolutely” nothing wrong.)

Republicans have expressed concern that if Greitens is their Senate nominee, they could well lose a seat that, based on recent presidential voting patterns, should be an easy hold for them. But many of those same Republicans admit that they may not be able to stop Greitens from winning.

While Missouri is clearly the stickiest wicket for McConnell – and Republicans more generally – contested primaries in Ohio, Pennsylvania and North Carolina all present some level of political peril for the likes of McConnell, depending on who the party chooses to nominate.

Looming over all this is former President Donald Trump, who has made clear that he plans to be actively involved in the 2022 primary season. Trump and McConnell are already on opposite sides of the Alaska Senate race, for instance, with McConnell supporting Sen. Lisa Murkowski and Trump backing challenger Kelly Tshibaka.

The Point: Things looks very good for McConnell and Senate Republicans. But Trump and the GOP base voters who are loyal to him represent a massive x-factor that could badly complicate the party’s math.